Methods of using chlamydia vaccine for preventing and treating bovine diseases

ABSTRACT

Method of using a modified live Chlamydia-chicken embryo origin vaccine for prevention and treatment of disease processes creating or induced by Chlamydia organisms in aminals of the bovine species.

BACKGROUND OF THE INVENTION

1. Field of Use

This invention relates generally to vaccines for veterinary use. Inparticular, it relates to Chlamydia vaccines useful for prevention andtreatment of disease processes created or induced by Chlamydia organismsin mammalians other than felines, particularly those of the bovinespecies, and to methods for immunizing and treating such animals withsuch vaccines.

2. Description of the Prior Art

Various strains of the Chlamydia psittaci organism(psittacosis-lymphogranuloma group) have been reported frequently asinvolved in various mammalian and avian disease processes. The pathologydescribed includes the following disease processes: enzootic abortion inewes, epizootic bovine abortion, feline pneumonitis,psittacosis-ornithosis, sporadic bovine encephalomyelitis, transmissibleserositis in sheep, calves and swine, bovine respiratory diseasecomplexes, enzootic pneumonia in calves, neonatal diarrhea of calves,polyarthritis in sheep and others.

The "Merck Veterinary Manual", Fourth Edition, published by Merck & Co.,Inc. of Rahway, N.J., U.S.A. (1973) provides specific descriptions ofthe aforementioned and other related pathologies, the occurrence ofChlamydial organisms in connection therewith, the recommended forms oftreatment, and the chemotherapeutical agents known and recommended foruse therewith, especially at pages 166, 272, 274, 277, 322, 375, 385 and879, as well as elsewhere.

The following references designated numbers 1 through 16 provide furtherinformation about such diseases and their treatment.

1. Boidin, A. G., Cordy, D. R., and Adler, H. E.: A Pleuropneumonia-likeOrganism and a Virus in Ovine Pneumonia in California. Cornell Vet., 48,(1959): 410-430.

2. Edward, A. G., Mills, G. D., and Calhoon, J. R.: Production ofColostrum-Deprived Specific Pathogen-Free Calves. Lab. Anim. Care, 17,(1967): 103-109.

3. Eugster, A. K., and Storz, J.: Pathogenetic Events in IntestinalChlamydial Infections Leading to Polyarthritis in Calves. J. Infect.Dis., 123, (1971): 41-50.

4. Gimenez, D. F.: Staining Rickettsiae in Yolk-Sac Cultures. StainTechnol., 39, (1964): 135-140.

5. Kawakami, Y., Omori, T., Fukuhara, S., Tokuda, G., Ishii, S., andMatumoto, M.: Studies on the Disease of Cattle Caused by aPsittacosis-Lymphogranuloma Group Virus (Miyagawanella). VII. Isolationof a Virus, Identified as a Member of the Psittacosis-LymphogranulomaGroup of Viruses, from Feces of Cattle. Jap. J. Exptl. Med., 25, (1955):51-63.

6. Page, L. A.: Proposal for the Recognition of Two Species in the GenusChlamydia Jones, Rake and Stearns, 1945. Internat. J. Sys. Bact., 18,(1968): 51-66.

7. Reed, C. J., and Muench, M.: A Simple Method for Estimation of FiftyPercent Endpoints. Am. J. Hyg., 27, (1938): 493-497.

8. Smith, P. C., Cutlip, R. C., and Page, L. A.: Pathogenicity of aStrain of Chlamydia psittaci of Bovine Intestinal Origin for NeonatalCalves. Am. J. Vet. Res., 34, (May, 1973): In press.

9. Storz, J., Collier, J. R., Eugster, A. K., and Altera, K. P.:Intestinal Bacterial Changes in Chlamydia-induced Primary Enteritis ofNewborn Calves. Ann. New York Acad. Sci., 176, (1971): 162-175.

10. Storz, J., Eugster, A. K., Altera, K. P., and Olander, H. J.:Behavior of Different Bovine Chlamydial Agents in Newborn Calves. J.Comp. Path. & Therap., 81, (1971): 299-307.

11. Storz, J., Marriott, M. E., and Winterer, B. I.: Detection andSeparation of Simultaneous Enterovirus and Intestinal ChlamydialInfection of Calves. Zentralbl. Bakt. (Orig.), 210, (1969): 75-81.

12. York, C. J., and Baker, J. A. A New Member of thePsittacosis-Lymphogranuloma Group of Viruses that Causes Infection inCalves. J. Exptl. Med., 93, (1951): 587-604.

13. York, C. J., and Baker, J. A.: Miyagawanella bovis Infection inCalves. Ann. New York Acad. Sci., 66, (1956): 210-214.

14. Journal of the South African Vet Association (1977), Vol. 48, p.261. It mentions that "abortions in sheep and cattle is well controlledby vaccination, but as yet no effective vaccine for the protection ofthe newborn has been developed".

15. Deutsche Tieranztlicke Wochenschrift (1975), Vol. 82, pp. 221 Itstates that two inactivated vaccines--"were tested on 16,581 sheep. Theeffectiveness of immediate vaccination of pregnant, including abortinganimals, was therefore proved for both vaccines".

16. Journal of the AVMA (1974), Vol. 165, No. 8, pp. 689 It describesthe use (or refers to the use) of an inactivated vaccine.

Heretofore, the above-referred to disease processes have been treated ina conventional manner by means of chemotherapeutic agents, withparticular success experienced by the use of high levels oftetracyclines orally or intravenously administered over prolongedperiods of time. However, insofar as applicant is aware, there is noknown vaccine which is commercially available for the prevention ortreatment of these disease processes in any species of animal, otherthan in felines and particularly, there is no teaching or recommendationto use live or modified live vaccine in bovines.

An example of a commercially available vaccine for immunization againstand prevention of feline pneumonitis is Feline Pneumonitis Vaccine,Modified Live Chlamydia-Chicken Embryo Origin (trade name PSITTACOID)produced for veterinary use only under U.S. Veterinary License No. 195-Afor immunization of cats against Chlamydia psittaci by FrommLaboratories, Inc., Grafton, Wisc. 53024, U.S.A. The recommended dosageand administration for cats is as follows: Rehydrate each 1 cc vial ofvaccine with 1 cc of diluent and inject intramuscularly orsubcutaneously. Vaccinate healthy cats of any age with one dose exceptthat if the animal is less than 12 weeks of age a second dose should begiven at 12 to 16 weeks of age. Annual revaccination with a single doseis recommended. Each 1 cc vial of vaccine contains the vaccine indesiccated form containing 10⁵.1 (at least 100,000 plus) modified liveorganisms which is to be diluted with a sterile diluent such asdistilled water.

The aforementioned conventional treatment of bovines, for example,suffering from Chlamydial infections by means of chemotherapeuticalagents is generally satisfactory, but has the drawbacks of beingrelatively time-consuming, expensive, and lacking long-termeffectiveness. For example, the conventional treatment of an individualanimal typically involves administration of recommended dosages oftetracyclines over a period of five or more consecutive days followed bysubsequent observations at less frequent intervals to ascertaintreatment effectiveness. Furthermore, a successfully treated individualanimal remains a carrier of the disease organism and is itselfsusceptible to reoccurrence of the disease, as well as being a source ofinfection to other animals in the herd. Such treatment, therefore, iscostly from the standpoint of veterinary services required and asregards the type and quantity of medication.

While the foregoing factors generally point to the desirability ofdiscovering a more economical and effective control regime forChlamydial infections in agricultural animals, particularly of those ofthe bovine species, none has heretofore been forthcoming for a varietyof reasons. For example, historical experience and classical theory inthe science and practice of veterinary medicine indicates thatimmunizing agents and methods of treatment involving the same may besuccessfully employed with one species of animal but are not necessarilyeffective, safe, or even available for another species. Indeed, notinfrequently, whereas beneficial results may occur in one species,unpredictable detrimental results can and often do occur in others. Thisfact has led to the development of different points of view and schoolsof thought within the profession regarding the desirability and possibleeffectiveness of using specific agents on different species.Furthermore, it is very often not possible to perform any studies,experiments or tests to establish effectiveness or non-effectiveness,especially those involving large numbers beef or dairy cattle, nimalssuch as where the possibility of risk or failure may not only be costlyand inconclusive, but totally disastrous.

SUMMARY OF THE INVENTION

Applicant reasoned that vaccination would provide more medicaleffectiveness in that it would prevent occurrence of the diseases andalso operate as a form of therapy after onset of the disease. Applicantdiscovered that the aforementioned Feline Pneumonitis Vaccine can beused to treat dairy cattle known to be infected with the chlamydialorganisms, and can also be used to treat new born calves to prevent thedisease as well as to treat the inherited (congenital) from thereof.

Thus, applicant discovered that a chlamydia vaccine can be administeredto, although not so limited, the bovine species to prevent, inhibit andlessen the severity of Chlamydial infections. More particularly,applicant has found that the Feline Pneumonitis Vaccine is useful forprevention and treatment of disease processes created or induced by theChlamydia organisms in larger animals, especially those of the bovinespecies. The vaccine may be administered in specified dosages atspecific intervals of time.

The route of administration is preferably parenteral. While not solimited, it has been found preferably to use deep intramuscularinjection of 1 ml of commercially available Feline Pneumonitis Vaccine,Modified Live Chlamydia-Chicken Embryo Origin (containing 10⁵.1 modifiedlive organism per 1 ml of desiccated vaccine), (trade name PSITTACOID),manufactured by Fromm Laboratories, Inc., Grafton, Wisc. 53024, U.S.A.,U.S. Veterinary License No. 195-A, dissolved in 1 cc of sterile diluentsuch as distilled water. Insofar as is known, the Chlamydia organism iscapable of producing interfon antibodies which means antibody protectionis stimulated at the cell level at the point of challenge. It is alsopossible to produce localized antibodies in the respiratory system ofbovines and other species if given as a nasal spray since this is adirect way to reach the respiratory system.

The schedule of vaccination is, but not limited to, one dose (one ml ofdesiccated vaccine dissolved in 1 ml of diluent) at birth, with threesuccessive doses (each dose comprising one ml of desiccated vaccinedissolved in 1 ml of diluent) at monthly intervals, followed by annualbooster vaccinations of the same dosage.

A schedule of vaccination involving one dose at birth, with furtherdoses at intervals of one week for four weeks gave very good success.

Direct introduction of the vaccine into the respiratory tract, as forexample, by intra-nasal introduction by nasal spray is particularlyuseful to treat animals suffering from respiratory involvement inducedby the chlamydia organisms. This mode of immunization and treatment maybe used alone or in conjunction with other therapy for the respiratoryailment.

Illustrative of the applicant's invention is the use of the vaccine totreat animals in a dairy herd. Calves were innoculated at birth using 1cc dose of the vaccine in desiccated form and containing 10⁵.1 modifiedlive organisms and dissolved in 1 cc of diluent (distilled water) andinjected in the muscle of the calves, followed by three additional dosesof the same potency and constituency at monthly intervals. Successfulimmunization against the Chlamydial organism resulted. Calves ratherthan adult animals were chosen for the initial experiment in order toobtain an early indication of possible toxic affects of the vaccine,since calves would be more susceptible to toxicity. Since there were nountoward problems associated with the vaccine in innoculatingsuccessively born calves in this first herd to be innoculated, thesafety and effectiveness of the vaccine was further demonstrated bysubsequently vaccinating over 2,000 calves from hundreds of dairy herdsusing the same dosage for each injection and injecting at the same, aswell as at different intervals of time.

Not by way of limitation, but as shown in greater detail the use ofapplicant's invention, the following experiments are representative ofthe results achieved.

EXAMPLE I

A herd of dairy cattle in the State of Wisconsin, known to be infectedwith the Chlamydia organism after laboratory confirmation, had sufferedsevere problems for many years, including abortions, pneumonia,encephalomegaly, arthritis, serositis and neonatal diarrhea. Followingthe death of six consecutive neonatal calves due to pneumonia and/orenteritis during the late summer and early fall, the applicant commencedintramuscularly innoculating all calves the day they were born with theaforementioned Feline Pneumonitis Vaccine initially using a 1 cc dose ofvaccine dissolved in 1 cc of diluent, following by three additionaldoses of the same potency and constituency at monthly intervals. Withinapproximately one year from the commencement of the vaccination program,34 calves had been born in this herd and were vaccinated as explainedabove. Of the 34 calves vaccinated, only three calves died; one frompneumonia, one from congenital deformity, and one because of prematurebirth as a twin. In connection with EXAMPLE I, the applicant observedclinical evidence that the calves in this herd were in all probabilityborn with a greater or lesser degree of Chlamydial infection and thesymptoms thereof increased rapidly during the first 24 to 96 hours afterbirth. The vaccinated calves, except the three which died, fullyrecovered from the infection.

EXAMPLE II

A herd of Montana beef cows consisting of 300 stock cows were clinicallydiagnosed in the spring as suffering from a Chlamydial infection whichappeared specifically as pneumonia accompanied by diarrhea in 20 calvesapproximately eight weeks of age. Of these 20 calves, the calves wereselected at random, and were given intramuscular vaccinations with theaforementioned Feline Pneumonitis Vaccine of the aforementioned dosageweekly, for a total of four doses. After the first vaccination therewere no observable changes. However, within 24 hours after the secondvaccination, the diarrhea ceased, and the pneumonia symptoms remarkablyimproved during the first week. After the fourth vaccination, it was notpossible to differentiate the ten vaccinated calves from calves that hadnever been ill. Four of the ten calves selected at random were initiallyvery ill, and were expected to die. However, these four calves allcompletely recovered. The ten unvaccinated calves of the original 20calves became stunted and never grew properly.

EXAMPLE III

Two young adult dairy cows in a Wisconsin herd suffered from along-standing lameness due to swollen posterior, hock, and carpaljoints. This lameness was clinically diagnosed as Chlamydia psittaciinfection. In spring, after one intramuscular injection of theaforementioned Feline Pneumonitis Vaccine of the aforementioned dosage,following by another similar injection ten days later, both cows showedcomplete recovery from the lameness within fourteen days of this secondinjection and have shown no further symptoms.

EXAMPLE IV

In summer, two young adult dairy cows in a Wisconsin herd suffered fromchronic bronchitis with frequent dry coughs which was diagnosed asChlamydia psittaci infection. An intramuscular injection of theaforementioned Feline Pneumonitis Vaccine of the aforementioned disagewas given, followed by a second such injection ten days later. Completerecovery from the coughing appeared within 48 hours following the secondinjection. However, there was a relapse within one week after the lastinjection, but with coughing of less frequency and severity and nofurther treatment followed. However, these animals were observed shortlybefore the time of filing of this application and were found to beremaining stable in view of the fact that they had suffered permanentlung damage.

EXAMPLE V

In summer, a herd of 120 veal calves two weeks old were vaccinated oncefor Infectious Bovine Rhinotrackeitis, Bovine Virus Diarrhea, and Parainfluenza-3. Sixty of these calves were also vaccinated once with theaforementioned Feline Pneumonitis Vaccine of the aforementioned dosage.The herd attendant was not told which calves were vaccinated with theFeline Pneumonitis Vaccine and four weeks later, when the herd wasexamined by applicant, the attendant stated there were fewer respiratoryand enteric problems in sixty calves, which calves were then determinedto be those that also had received the Feline Pneumonitis Vaccine. Thesecalves were then clinically examined by the applicant and the notedimprovements were verified.

EXAMPLE VI

In the fall, four calves, ten weeks old were suffering from chronicpneumonia. These calves were from a Wisconsin dairy herd known bylaboratory confirmation to be infected with the Chlamydia organism. Allfour calves were given one dose of the aforementioned Feline PneumonitisVaccine intramuscularly. All four calves showed complete remission ofsymptoms in 72 hours. No further symptoms of disease developed in thesecalves.

EXAMPLE VII

In the summer, a two year old heifer from a Wisconsin herd known bylaboratory confirmation to be infected with the Chlamydia organismdeveloped moderate central nervous symptoms fourteen days before she wasdue to calve. These symptoms included loss of appetite and generallethargy. After she calved the symptoms became more aggravated andtreatment was instituted, on the third day, post partum using acceptedchemotherapeutic agents. She was completely unresponsive to thistreatment over several days. Ten days after she calved, she was givenone dose of the aforementioned Feline Pneumonitis Vaccineintramuscularly. In twenty-four hours, she was completely asymptomaticand has remained so.

EXAMPLE VIII

In the summer, a calf was born in a Wisconsin dairy herd known bylaboratory confirmation to be infected with the Chlamydia organism.Severe lacramation, and front leg joint swelling were noted. The calfwas given one dose of the aforementioned Feline Pneumonitis Vaccineintramuscularly and no other treatment was given. In 24 hours thehyperlacramation ceased, in seven days the joints were normal, and thecalf remained normal. 9n

I claim:
 1. A method of immunizing and treating bovines againstchlamydia psittaci which comprises parenterally administering modifiedlive Chlamydia feline pneumonitis vaccine to the bovines to stimulatethe production of antibodies therein.
 2. The method according to claim1, wherein the vaccine is a modified live chlamydia vaccine of chickenembryo origin.
 3. The method according to claim 2 wherein at least 1 mlof vaccine is administered.
 4. The method according to claim 3 whereinthe vaccine is administered intramuscularly.
 5. The method according toclaim 2 wherein at least 1 ml of the vaccine is administered followed bya second administration of at least 1 ml of the vaccine about ten dayslater.
 6. The method according to claim 2 wherein at least 1 ml of thevaccine is administered followed by three successive administrations ofat least 1 ml of the vaccine at one month intervals.
 7. The methodaccording to claim 5 wherein the vaccine is administeredintramuscularly.
 8. The method according to claim 6 wherein vaccine isadministered intramuscularly.
 9. A method of immunizing and treating ananimal of the bovine species against chlamydia psittaci which comprisesparenterally administering modified live chlamydia feline pneumonitisvaccine to said bovine to stimulate the production of antibodiescomparable to those produced by natural infections when parenterallyintroduced into a non-immune animal of the same species withoutintroducing the usual pathological symptoms of disease due to chlamydiapsittaci.
 10. The method according to claim 9 wherein the vaccine isadministered intramuscularly.
 11. The method according to claim 10wherein at least 1 ml of the vaccine is so administered.
 12. The methodaccording to claim 10 wherein at least 1 ml of the vaccine isadministered followed by administration of at least 1 ml of the vaccineabout ten days later.
 13. The method according to claim 10 wherein atleast 1 ml of the vaccine is administered followed by three successiveadministrations of at least 1 ml of the vaccine at one month intervals.14. A method of immunizing and treating bovines against chlamydiapsittaci which comprises administering by the respiratory route modifiedlive chlamydia feline pneumonitis, vaccine to the bovines to stimulatethe production of antibodies therein.
 15. A method of immunizing andtreating an animal of the bovine species against chlamydia psittaciwhich comprises administering by the respiratory route modified livechlamydia feline pneumonitis vaccine to said bovine to stimulate theproduction of antibodies comparable to those produced by naturalinfections when parenterally introduced into a non-immune animal of thesame species without introducing the usual pathological symptoms ofdiseases due to chlamydia psittaci.
 16. The method set forth in claim 9wherein said chlamydia vaccine is of chicken embryo origin.
 17. Themethod set forth in claim 15 wherein said chlamydia vaccine is ofchicken embryo origin.